The class
Plasma CETP causes pancreatic beta cell dysfunction via islet cholesterol accumulation in mice (Nutr Metab 2016)
Original title: The effect of cholesteryl ester transfer protein on pancreatic beta cell dysfunction in mice
Adipose tissue-specific CETP-transgenic mice, which have high circulating CETP levels, were used to test whether plasma CETP damages pancreatic beta cell function through tissue cholesterol accumulation. The transgenic mice showed glucose intolerance, lower plasma insulin, and reduced glucose-stimulated insulin secretion from isolated islets despite increased insulin sensitivity, alongside significantly increased free cholesterol and reduced islet number and size. Genes involved in beta cell proliferation and differentiation were down-regulated while inflammation and endoplasmic reticulum stress genes were up-regulated, consistent with increased beta cell apoptosis. The authors conclude plasma CETP causes free cholesterol accumulation in islets that contributes to beta cell dysfunction, proposing CETP inhibition as a potential protective strategy against diabetes-related dyslipidemia.
Original abstract
Background: Cholesterol accumulation causes pancreatic beta cell lipotoxicity and dysfunction. Cholesteryl ester transfer protein (CETP) plays an important role in blood lipid homeostasis. However, its role in tissue lipid metabolism remains unclear. We hypothesized that plasma CETP impact cholesterol homeostasis in the beta cells, thus damaging their functions.
Methods: The adipose tissue-specific CETP expression transgenic (aP2-CETPTg) mice, characterized by high CETP levels in the circulation, were used in this study. Pancreatic islet cholesterol and beta cell function were assessed in mice. We further measured mRNA levels of the genes involved in beta cell proliferation and differentiation, inflammation and cholesterol metabolism. TUNEL assay was applied to investigate beta cell apoptosis in islets.
Results: The aP2-CETPTg mice exhibited glucose intolerance, lower plasma insulin concentrations but increased insulin sensitivity compared with wild type mice. In addition, glucose-stimulated insulin secretion from isolated pancreatic islets significantly decreased, and free cholesterol significantly increased. Moreover, the number and size of islets from aP2-CETPTg mice were significantly decreased. Genes involved in beta cell proliferation, such as Pdx1 and BETA2, were down-regulated; genes involved in inflammation and ER stress, such as IL-1β, CHOP, and Xbp1 were up-regulated, in line with an increase of beta cell apoptosis.
Conclusions: Plasma CETP causes free cholesterol accumulation in islets which could contribute to beta cell dysfunction. Thus, CETP inhibition could be a novel protective strategy for dyslipidemia related to diabetes and obese.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.